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Depressive and anxiety disorders are highly comorbid, which has been theorized to be due to an underlying internalizing vulnerability. We aimed to identify groups of participants with differing vulnerabilities by examining the course of internalizing psychopathology up to age 45.
Methods
We used data from 24158 participants (aged 45+) in 23 population-based cross-sectional World Mental Health Surveys. Internalizing disorders were assessed with the Composite International Diagnostic Interview (CIDI). We applied latent class growth analysis (LCGA) and investigated the characteristics of identified classes using logistic or linear regression.
Results
The best-fitting LCGA solution identified eight classes: a healthy class (81.9%), three childhood-onset classes with mild (3.7%), moderate (2.0%), or severe (1.1%) internalizing comorbidity, two puberty-onset classes with mild (4.0%) or moderate (1.4%) comorbidity, and two adult-onset classes with mild comorbidity (2.7% and 3.2%). The childhood-onset severe class had particularly unfavorable sociodemographic outcomes compared to the healthy class, with increased risks of being never or previously married (OR = 2.2 and 2.0, p < 0.001), not being employed (OR = 3.5, p < 0.001), and having a low/low-average income (OR = 2.2, p < 0.001). Moderate or severe (v. mild) comorbidity was associated with 12-month internalizing disorders (OR = 1.9 and 4.8, p < 0.001), disability (B = 1.1–2.3, p < 0.001), and suicidal ideation (OR = 4.2, p < 0.001 for severe comorbidity only). Adult (v. childhood) onset was associated with lower rates of 12-month internalizing disorders (OR = 0.2, p < 0.001).
Conclusions
We identified eight transdiagnostic trajectories of internalizing psychopathology. Unfavorable outcomes were concentrated in the 1% of participants with childhood onset and severe comorbidity. Early identification of this group may offer opportunities for preventive interventions.
There is a substantial proportion of patients who drop out of treatment before they receive minimally adequate care. They tend to have worse health outcomes than those who complete treatment. Our main goal is to describe the frequency and determinants of dropout from treatment for mental disorders in low-, middle-, and high-income countries.
Methods
Respondents from 13 low- or middle-income countries (N = 60 224) and 15 in high-income countries (N = 77 303) were screened for mental and substance use disorders. Cross-tabulations were used to examine the distribution of treatment and dropout rates for those who screened positive. The timing of dropout was examined using Kaplan–Meier curves. Predictors of dropout were examined with survival analysis using a logistic link function.
Results
Dropout rates are high, both in high-income (30%) and low/middle-income (45%) countries. Dropout mostly occurs during the first two visits. It is higher in general medical rather than in specialist settings (nearly 60% v. 20% in lower income settings). It is also higher for mild and moderate than for severe presentations. The lack of financial protection for mental health services is associated with overall increased dropout from care.
Conclusions
Extending financial protection and coverage for mental disorders may reduce dropout. Efficiency can be improved by managing the milder clinical presentations at the entry point to the mental health system, providing adequate training, support and specialist supervision for non-specialists, and streamlining referral to psychiatrists for more severe cases.
Biomarkers for psychiatric disorders are critical for patient stratification, premorbid diagnosis and personalized treatment. Our aim is to identify protein biomarkers for anxiety disorders by comparing the synaptic proteomes of a well-established mouse model of high (HAB), normal (NAB) and low (LAB) anxiety-related behavior.
Methods
We have compared protein expression levels using 15N metabolic labeling and quantitative proteomics. Mice were metabolically labeled through feeding with a 15N-enriched diet. Synaptosomes from unlabeled HAB and LAB mice were then compared with synaptosomes from 15N labeled NAB mice by quantitative mass spectrometry. Protein expression differences were validated with Western blots, enzymatic assays and in silico pathway analysis.
Results
We have identified numerous protein expression differences between HAB and LAB synaptosome proteomes. We observed alterations in energy metabolism pathways such as the Krebs cycle as well as in mitochondrial function. Furthermore, we detected changes in transport and phosphorylation processes.
Conclusions
We present an accurate proteomics platform for biomarker discovery in psychiatric disorders. We identified candidate biomarkers and pathways involved in anxiety pathophysiology. Our data provide the basis for the establishment of a biomarker panel that will shed light on anxiety pathophysiology and can be applied for optimal therapeutic intervention.
The treatment of depressive phases of bipolar disorder is challenging. Electroconvulsive therapy (ECT) is generally considered to be the most effective treatment even if there are no randomized controlled trials (RCT) of ECT in bipolar depression. The safety of ECT is well documented, but there are some controversies as to the cognitive side effects.
Objectives
To compare the effects and side effects of ECT with pharmacological treatment in treatment resistant bipolar depression. Cognitive changes during the treatment will be measured, as well as quality of life.
Method
A prospective, randomised controlled multi-centre trial. 6- week acute treatment trial with 7 clinical assessments. Follow up visit at 26 weeks or until remission (max 52 weeks). A neuropsychological test battery designed to be sensitive to changes in cognitive function will be used.
Setting
Nine study centres across Norway, all acute psychiatric wards
Sample
132 patients aged 18 and over, who fulfil criteria for treatment resistant depression in bipolar disorder, MADRS score of at least 25 at baseline
Intervention
Intervention group: 3 sessions per week for up to 6 weeks, total up to 18 sessions. Control group: algorithm-based pharmacological treatment as usual.
Results
Six departments have included 43 patients since start in May 2008.
Conclusion
This study is the first randomized controlled trial that aims to investigate whether ECT is better than pharmacological treatment as usual in treatment resistant bipolar depression. Possible long lasting cognitive side effects will be evaluated. The study is investigator initiated, without support from industry.
Screening scales can be useful in searching for common mental disorders in primary care and in tracking relevant prevalence and correlates in community surveys. However, it is important to document their validity, before using them. We developed Italian versions of the widely-used K10 and K6 screening scales following the WHO forward-translation and back-translation protocol. To evaluate their effectiveness as screens for DSM-IV 12-month mood or anxiety disorders and “serious mental illness” (SMI), the scales were validated in a two-stage clinical reappraisal survey. In the first-phase, the scales were administered to 605 people. In the second-phase, a sub-sample of 147 first-phase respondents over-sampling screened positives was administered the 12-month version of the Structured Clinical Interview for DSM-IV Axis I Disorders as a clinical gold standard. Performance of the scales in screening for chosen disorders was assessed by calculating area under the receiver operating characteristic curve and stratum-specific likelihood ratios. Both the K10 and K6 performed well in detecting DSM-IV mood disorders, anxiety disorders, and serious mental illness (SMI), with areas under the curve (AUCs) (95% CIs) between 0.82 (0.75–0.89) and 0.91 (0.85–0.96). The Italian versions of the K6 and K10 scales have good psychometric properties, making them attractive inexpensive screens for mood disorders, anxiety disorders, and SMI.
Electroconvulsive therapy (ECT) is a treatment alternative in bipolar disorder (BD) depression. Cognitive side effects are the major concern limiting its use.
Objectives
We present data from the Norwegian randomized controlled trial of ECT in treatment resistant depression in bipolar disorder.
Aims
To compare effects on cognitive function of ECT or algorithm based pharmacological treatment at the end of a six-week acute, BD depression treatment trial.
Methods
Prospective, randomised controlled multi-centre, six-week acute treatment trial. Pre- and post-treatment assessments with the MATRICS Consensus Cognitive Battery (MCCB); a neuropsychological test battery designed to be sensitive to changes in cognitive function.
Sample
N = 51 patients ≥ 18 years fulfilling criteria for treatment resistant BD depression (MADRS score ≥ 25).
Intervention
ECT group: Three sessions per week for up to six weeks, total up to 18 sessions, and right unilateral electrode placement. Algorithm-based pharmacological treatment group: Based on Goodwin & Jamison, 2007.
Results
Both groups showed a net gain on MCCB scores without significant differences between the study groups. Mean change in MCCB composite T-score was 4.0 (5.7) in the ECT group and 2.7 (3.6) in the pharmacological group (F = 0.78, eta2 = 0.021, p = 0.383).
Conclusion
In treatment resistant BD depression ECT and algorithm-based pharmacological treatment have comparable effects on cognitive function assessed with the MATRICS.
Neuroimaging studies of depression have demonstrated treatment-specific changes involving the limbic system and regulatory regions in the prefrontal cortex. While these studies have examined the effect of short-term, interpersonal or cognitive-behavioural psychotherapy, the effect of long-term, psychodynamic intervention has never been assessed. Here, we investigated recurrently depressed (DSM-IV) unmedicated outpatients (N=16) and control participants matched for sex, age, and education (N=17) before and after 15 months of psychodynamic psychotherapy. Participants were scanned at two time points, during which presentations of attachment-related scenes with neutral descriptions alternated with descriptions containing personal core sentences previously extracted from an attachment interview. Outcome measure was the interaction of the signal difference between personal and neutral presentations with group and time, and its association with symptom improvement during therapy. Signal associated with processing personalized attachment material varied in patients from baseline to endpoint, but not in healthy controls. Patients showed a higher activation in the left anterior hippocampus/amygdala, subgenual cingulate, and medial prefrontal cortex before treatment and a reduction in these areas after 15 months. This reduction was associated with improvement in depressiveness specifically, and in the medial prefrontal cortex with symptom improvement more generally. This is the first study documenting neurobiological changes in circuits implicated in emotional reactivity and control after long-term psychodynamic psychotherapy.
According to the most widely influential treatment guidelines from the National Institute for Health and Clinical Excellence and the American Psychiatric Association, existing evidence for adult AN treatment is weak, and more treatment studies are needed.
Objectives/aims
The primary objective of this project is to gain knowledge about the effectiveness of CBT-E in the treatment of Anorexia Nervosa (AN). Secondary objectives are to prospectively examine baseline predictors of treatment outcome/drop-out and to examine variables related to treatment process and patient engagement as predictors of outcome/drop-out. Thirdly, in a multidisciplinary approach, to focus on selected pathophysiological mechanisms including disturbed neuropsychological functioning, changes in the gut microbiota, immunological and genetic measures in patients with severe AN in different stages of the disease, and further to investigate to what extent they are related to treatment outcome.
Methods
The sample consists of patients aged ≥ 16 years with AN admitted to outpatient treatment (CBT-E) at Section for Eating Disorders, Haukeland University Hospital, Bergen, Norway. Outcome measures include BMI, self-reported eating disorder symptoms (EDE-Q), depression (BDI), anxiety (BAI) general psychiatric symptomatology (SCL-90-R, M.I.N.I 6.0), health related quality of life (CIA, RAND-36), physical activity (accelerometers) and neuropsychological functioning. The main measurement points are at the start of treatment, 3 months, end of treatment and one year follow-up. Baseline predictors of treatment outcome and drop-out will be examined as well as the association between early adherence, behavioral change, therapeutic alliance and treatment outcome. In addition biochemical, genetic and bacteriological assessments will be conducted.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Intermittent explosive disorder (IED) is characterised by impulsive anger attacks that vary greatly across individuals in severity and consequence. Understanding IED subtypes has been limited by lack of large, general population datasets including assessment of IED. Using the 17-country World Mental Health surveys dataset, this study examined whether behavioural subtypes of IED are associated with differing patterns of comorbidity, suicidality and functional impairment.
Methods
IED was assessed using the Composite International Diagnostic Interview in the World Mental Health surveys (n = 45 266). Five behavioural subtypes were created based on type of anger attack. Logistic regression assessed association of these subtypes with lifetime comorbidity, lifetime suicidality and 12-month functional impairment.
Results
The lifetime prevalence of IED in all countries was 0.8% (s.e.: 0.0). The two subtypes involving anger attacks that harmed people (‘hurt people only’ and ‘destroy property and hurt people’), collectively comprising 73% of those with IED, were characterised by high rates of externalising comorbid disorders. The remaining three subtypes involving anger attacks that destroyed property only, destroyed property and threatened people, and threatened people only, were characterised by higher rates of internalising than externalising comorbid disorders. Suicidal behaviour did not vary across the five behavioural subtypes but was higher among those with (v. those without) comorbid disorders, and among those who perpetrated more violent assaults.
Conclusions
The most common IED behavioural subtypes in these general population samples are associated with high rates of externalising disorders. This contrasts with the findings from clinical studies of IED, which observe a preponderance of internalising disorder comorbidity. This disparity in findings across population and clinical studies, together with the marked heterogeneity that characterises the diagnostic entity of IED, suggests that it is a disorder that requires much greater research.
Epidemiological studies indicate that individuals with one type of mental disorder have an increased risk of subsequently developing other types of mental disorders. This study aimed to undertake a comprehensive analysis of pair-wise lifetime comorbidity across a range of common mental disorders based on a diverse range of population-based surveys.
Methods
The WHO World Mental Health (WMH) surveys assessed 145 990 adult respondents from 27 countries. Based on retrospectively-reported age-of-onset for 24 DSM-IV mental disorders, associations were examined between all 548 logically possible temporally-ordered disorder pairs. Overall and time-dependent hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards models. Absolute risks were estimated using the product-limit method. Estimates were generated separately for men and women.
Results
Each prior lifetime mental disorder was associated with an increased risk of subsequent first onset of each other disorder. The median HR was 12.1 (mean = 14.4; range 5.2–110.8, interquartile range = 6.0–19.4). The HRs were most prominent between closely-related mental disorder types and in the first 1–2 years after the onset of the prior disorder. Although HRs declined with time since prior disorder, significantly elevated risk of subsequent comorbidity persisted for at least 15 years. Appreciable absolute risks of secondary disorders were found over time for many pairs.
Conclusions
Survey data from a range of sites confirms that comorbidity between mental disorders is common. Understanding the risks of temporally secondary disorders may help design practical programs for primary prevention of secondary disorders.
Despite increased awareness that non-suicidal self-injury (NSSI) poses a significant public health concern on college campuses worldwide, few studies have prospectively investigated the incidence of NSSI in college and considered targeting college entrants at high risk for onset of NSSI.
Methods:
Using data from the Leuven College Surveys (n = 4,565; 56.8%female, Mage = 18.3, SD = 1.1), students provided data on NSSI, sociodemographics, traumatic experiences, stressful events, perceived social support, and mental disorders. A total of 2,163 baseline responders provided data at a two-year annual follow-up assessment (63.2% conditional response rate).
Results:
One-year incidence of first onset NSSI was 10.3% in year 1 and 6.0% in year 2, with a total of 8.6% reporting sporadic NSSI (1–4 times per year) and 7.0% reporting repetitive NSSI (≥ 5 times per year) during the first two years of college. Many hypothesized proximal and distal risk factors were associated with the subsequent onset of NSSI (ORs = 1.5–18.2). Dating violence prior to age 17 and severe role impairment in daily life were the strongest predictors. Multivariate prediction suggests that an intervention focused on the 10% at highest risk would reach 23.9% of students who report sporadic, and 36.1% of students who report repetitive NSSI during college (cross-validated AUCs =.70–.75).
Discussion:
The college period carries high risk for the onset of NSSI. Individualized web-based screening may be a promising approach for detecting young adults at high risk for self-injury and offering timely intervention.
To provide cross-national data for selected countries of the Americas on service utilization for psychiatric and substance use disorders, the distribution of these services among treatment sectors, treatment adequacy and factors associated with mental health treatment and adequacy of treatment.
Methods
Data come from data collected from 6710 adults with 12 month mental disorder surveys across seven surveys in six countries in North (USA), Central (Mexico) and South (Argentina, Brazil, Colombia, Peru) America who were interviewed 2001–2015 as part of the World Health Organization (WHO) World Mental Health (WMH) Surveys. DSM-IV diagnoses were made with the WHO Composite International Diagnostic Interview (CIDI). Interviews also assessed service utilization by the treatment sector, adequacy of treatment received and socio-demographic correlates of treatment.
Results
Little over one in four of respondents with any 12 month DSM-IV/CIDI disorder received any treatment. Although the vast majority (87.1%) of this treatment was minimally adequate, only 35.3% of cases received treatment that met acceptable quality guidelines. Indicators of social-advantage (high education and income) were associated with higher rates of service use and adequacy, but a number of other correlates varied across survey sites.
Conclusions
These results shed light on an enormous public health problem involving under-treatment of common mental disorders, although the problem is most extreme among people with social disadvantage. Promoting services that are more accessible, especially for those with few resources, is urgently needed.
Increased post-traumatic stress disorder (PTSD) rates have been documented in children exposed to war. However, the contribution of childhood adversities and environmental sensitivity to children's responses to adversities and trauma are still far from settled.
Aims
To evaluate the relative roles of war, childhood adversities and sensitivity in the genesis of PTSD.
Method
Data on childhood adversities and sensitivity was collected from 549 Syrian refugee children in Lebanon. PTSD symptoms were assessed using the PTSD Reaction Index.
Results
Although childhood adversities, war events and sensitivity were all significantly related to PTSD in bivariate analyses, multivariate analyses showed that childhood adversities were the most important variable in predicting PTSD. The effect of war on PTSD was found to be dependent on the interplay between childhood adversities and sensitivity, and was most prominent in highly sensitive children with lower levels of adversities; in sensitive children experiencing high levels of adversities, the effects of war exposure on PTSD were less pronounced.
Conclusions
When considering the effects of war on PTSD in refugee children, it is important to take account of the presence of other adversities as well as of children's sensitivity. Sensitive children may be more vulnerable to the negative effects of war exposure, but only in contexts that are characterised by low childhood adversities.
This paper updates Living with Mortality published in 2006. It describes how the longevity risk transfer market has developed over the intervening period, and, in particular, how insurance-based solutions – buy-outs, buy-ins and longevity insurance – have triumphed over capital markets solutions that were expected to dominate at the time. Some capital markets solutions – longevity-spread bonds, longevity swaps, q-forwards and tail-risk protection – have come to market, but the volume of business has been disappointingly low. The reason for this is that when market participants compare the index-based solutions of the capital markets with the customised solutions of insurance companies in terms of basis risk, credit risk, regulatory capital, collateral and liquidity, the former perform on balance less favourably despite a lower potential cost. We discuss the importance of stochastic mortality models for forecasting future longevity and examine some applications of these models, e.g. determining the longevity risk premium and estimating regulatory capital relief. The longevity risk transfer market is now beginning to recognise that there is insufficient capacity in the insurance and reinsurance industries to deal fully with demand and new solutions for attracting capital markets investors are now being examined – such as longevity-linked securities and reinsurance sidecars.
To investigate for the first time the determinants and barriers of seeking help for mental disorders in the Arab world based on a national study: Lebanese Evaluation of the Burden of Ailments and Needs Of the Nation (L.E.B.A.N.O.N).
Methods
A nationally representative (n = 2857) and multistage clustered area probability household sample of adults ≥18 years and older was assessed for lifetime and 12 months mental disorders using the Composite International Diagnostic Interview. In addition, detailed information was obtained on help- seeking behaviour and barriers to treatment.
Results
In total, 19.7% of the Lebanese with mental disorders sought any type of treatment: 91% of those who sought treatment did so within the health sector. Severity and perceived severity of disorders predicted seeking help, the highest being for panic disorder. The greatest barrier to seek help was low perceived need for treatment (73.9%). Stigma was reported to be a factor only in 5.9% of those who thought about seeking treatment. Eighty per cent of the Lebanese reported they would not be embarrassed if friends knew they were seeking help from a professional.
Conclusions
A small fraction of Lebanese seek help for their mental health problems: female gender, higher education and income are predictors of positive attitudes to help seeking. Severity and recognition of disorders, more than stigma, to get treatment seem to be the most important factors in determining help seeking. The findings underscore the importance of helping the public recognise mental health disorders.